ArticleThe Biochemical journal1997
Temperature-sensitive mRNA degradation is an early event in hepatocyte de-differentiation.
Article in The Biochemical journal, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 19 citations in OpenAlex.
- A comparative study of genome-wide transcriptional profiles of primary hepatocytes in collagen sandwich and monolayer cultures.Tissue engineering. Part C, Methods · 2010Article
- miR-194 is a marker of hepatic epithelial cells and suppresses metastasis of liver cancer cells in mice.Hepatology (Baltimore, Md.) · 2010Article
- 3D hepatic cultures simultaneously maintain primary hepatocyte and liver sinusoidal endothelial cell phenotypes.PloS one · 2010Article
- Generation of hepatocytes expressing functional cytochromes P450 from a pancreatic progenitor cell line in vitro.The Biochemical journal · 2003Article
- Disruption of endogenous regulator homeostasis underlies the mechanism of rat CYP1A1 mRNA induction by metyrapone.The Biochemical journal · 1998Article
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Authors and funding
4 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
The isolation and culture of metabolically active hepatocytes by proteolytic digestion of the extracellular matrix of the liver results in the transcriptional silencing of liver-specific genes encoding cytochromes P-450 (CYP) and albumin together with an induction of cellular RNase activity. The levels of albumin mRNA are maintained in cultured hepatocytes at similar levels to that present in the intact liver for at least 24 h, whereas the major constitutively expressed CYP2C11 mRNA is rapidly degraded. Hepatocytes heat-shocked at 40 degrees C during the isolation procedure (which results in an induction of heat-shock protein mRNA species) blocks the increase in RNase activity and abrogates the loss of CYP2C11 mRNA for at least 4 h. Cycloheximide-dependent inhibition of protein synthesis blocks the temperature-dependent induction of heat-shock proteins without affecting the protection afforded to CYP2C11 mRNA, indicating that CYP2C11 mRNA levels are not directly dependent on heat-shock protein induction and suggesting that the induction of RNase activity might be responsible for the specific loss of CYP2C11 mRNA in hepatocytes isolated at 37 degrees C. Differential rates of degradation of CYP2C11 transcribed in vitro and of albumin mRNA are observed in the presence of cellular extracts from cultured hepatocytes isolated at 37 degrees C (which have maximally induced levels of cellular RNase activity) but not in comparable extracts from cultured hepatocytes isolated at 40 degrees C, supporting the hypothesis that an RNase activity is induced in culture that specifically degrades CYP2C11 mRNA but not albumin mRNA. These results suggest that an early event in hepatocyte de-differentiation involves the induction of RNase activity in addition to transcriptional silencing of liver-specific genes and that the induced RNase activity demonstrates specificity within liver-specific gene products.
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